Obstetric Anal Sphincter Injury Care Bundle: A Quality Improvement Initiative.

INTRODUCTION AND HYPOTHESIS: The objective was to implement an evidence-based peri-partum care bundle for women sustaining obstetric anal sphincter injuries and to evaluate compliance with recommendations for antibiotics use, repair in the operating room, and follow-up before and after implementation. METHODS: This project was reviewed by the Institutional Review Board and determined to be exempt. A clinical care bundle containing education and standardized orders in the electronic medical record was implemented. Characteristics of pre- (October 2017 to September 2019) and post-intervention (October 2019 to August 2021) cohorts were compared and compliance with recommendations for antibiotics use, surgical repair location, and follow-up were evaluated. Chi-squared, Fisher's exact, ANOVA F, and Kruskal-Wallis tests were performed, as indicated. Significance level was p < 0.05. RESULTS: A total of 185 cases were identified. Seventy-five percent of women were nulliparous. Mean gestational age was 39 weeks. Pre- and post-intervention groups did not differ in age, BMI, race, parity, gestational age, comorbidities, birthweight, or delivery type. Ninety-eight cases were identified pre-implementation. Eighty-six (88%) had third-degree lacerations. Post-implementation, 87 cases were identified. Seventy (80%) had third-degree lacerations (p = 0.17). Recommended antibiotic-type use improved from 35% pre-implementation to 93% post-implementation (p < 0.001). Repair in the operating room was similar pre-implementation and post-implementation (16.0% vs 12.6%, p = 0.48). Post-partum follow-up within 2 weeks improved from 16.3% pre-implementation to 52.8% post-implementation and mean time to follow-up was shorter post-implementation than pre-implementation (18 vs 33 days; both p < 0.001). CONCLUSIONS: Implementation of an evidence-based peri-partum care bundle resulted in standardization of care in accordance with established recommendations. Compliance with recommendations for surgical repair in the operating room remained unchanged.

Use of a mobile health patient engagement technology improves perioperative outcomes in gynecologic oncology patients.

OBJECTIVE: To evaluate the impact of a mobile health patient engagement technology (PET) on postoperative outcomes in gynecologic oncology patients. METHODS: All gynecologic oncology patients undergoing laparotomy on an enhanced recovery program (ERP) were approached from July 2019 to May 2021 to enroll in a PET, which can be accessed by computer, tablet, or smart phone. This platform provides enhanced pre- and postoperative patient education and remote patient monitoring. Patients who elected to participate were provided with targeted education based on their age and comorbidities and were asked to complete daily health checks during the postoperative period. Participants in the PET were compared to patients who opted out as well as to a historical cohort from prior to PET implementation. Patient and procedure-level factors were recorded. The primary outcomes were length of stay (LOS) and 30-day readmission rate. Analysis was performed using SPSS v.26. RESULTS: 682 women met inclusion criteria during the study time; 347 in the PET group and 335 in the control group. Demographic and other factors including race, BMI (kg/m2), Charlson Comorbidity Index (CCI), surgical complexity, and insurance status were not different between the PET and control group; however, patients in the PET cohort were slightly younger (55.0 yo vs. 57.2 yo; p = 0.04). Patients in the PET group had a significantly shorter LOS (2.9 days vs. 3.6 days; p < 0.01) and lower readmission rate (4.3% vs. 8.6%; p < 0.01) when compared with the control group. CONCLUSIONS: Use of a PET in our gynecologic oncology patients decreased LOS by nearly one day despite an absence of differences in other demographic and surgical factors other than age. Furthermore, there was a 50% reduction in readmission rates in the PET group. The use of a PET allows for healthcare professionals to engage, evaluate, and treat patients in a way that improves perioperative care.

Standing on the shoulders of giants: Mentorship advice from leaders in the field.

This commentary is presenting opinions and advice on mentorship in the field of gynecologic oncology. Eleven academic gynecologic oncologists from across the country were interviewed and their thoughts about mentorship were recorded with recurring themes and ideas described in this commentary. Trust, respect, and mutual agreement on expectations were all described as vital to a functioning mentor/mentee relationship. Mentorship is critical for fellows and junior faculty to expand and uphold the standards of the field.

An enhanced recovery protocol decreases complication rates in high-risk gynecologic oncology patients undergoing non-emergent laparotomy.

OBJECTIVE: Enhanced recovery protocols are now established as the standard of care leading to improved perioperative outcomes and associated cost-benefits. The objective of this study was to evaluate the impact of an enhanced recovery program on complication rates in high-risk gynecologic oncology patients undergoing surgery. METHODS: This retrospective cohort study included gynecologic oncology patients with pathology-proven malignancy undergoing non-emergent laparotomy from October 2016 to December 2018 managed on an enhanced recovery protocol, and a control group from October 2015 through September 2016 prior to enhanced recovery protocol implementation. The primary outcome was complication rates in a high-risk population pre- and post-enhanced recovery protocol. High-risk patients were defined as those with obesity (body mass index >30 kg/m2) and/or age ≥65 years. Analysis was performed using Statistical Package for Social Sciences (SPSS) v.24. RESULTS: A total of 363 patients met the inclusion criteria: 104 in the control group and 259 in the enhanced recovery protocol group. Patient demographics, including age, body mass index, diagnosis, and performance status, were similar. Overall complication rates were less in the enhanced recovery protocol group (29% vs 53.8%; p<0.0001). The enhanced recovery protocol group had a shorter length-of-stay compared with control (3.3 vs 4.2 days; p<0.0001). The 30-day readmission rates were similar between the groups (9.6% vs 13.5%; p=0.19). In the enhanced recovery protocol group compared with control, complication rates were less in obese patients (29.4% vs 57.8%; p<0.0001), morbidly obese patients (20.9% vs 76.2%; p<0.0001), and age ≥65 (36.1% vs 57.1%; p<0.0001). The most common complications in the enhanced recovery protocol group were ileus (9.7%), pulmonary complications (2.7%), and blood transfusions (10.8%). CONCLUSIONS: Implementation of an enhanced recovery protocol decreases complication rates and length-of-stay in morbidly obese and geriatric patients with gynecologic malignancy without an increase in readmission rates.

The financial impact of an enhanced recovery after surgery (ERAS) protocol in an academic gynecologic oncology practice.

OBJECTIVE: To determine the financial impact of an enhanced recovery after surgery (ERAS) protocol in gynecologic oncology patients. METHODS: This study identified gynecologic oncology patients who were placed on the ERAS protocol after elective laparotomy from 10/2016-6/2017. A control group was identified from the year prior to ERAS implementation. Financial experts assisted in procuring data for these patient encounters, including payer status, direct and indirect costs, contribution margin, and length of stay (LOS). SPSS Statistics v. 24 was used for statistical analysis. RESULTS: 376 patients met criteria for inclusion: 179 in the ERAS group and 197 in the control group. Patient demographics were similar between the two cohorts. Payer status across the groups was not statistically significant in patients with private insurance (control 43.7% vs. ERAS 41.3%), Medicare (38.1% vs. 31.8%), or self-pay patients (12.2% vs. 15.1%). There was a significantly higher number of Medicaid patients in the ERAS group (6.1% vs. 11.7%; p = 0.05). Hospital direct costs ($5596 vs. 5346) and indirect costs ($5182 vs. $4954) per encounter were similar between groups. However, overall contribution margin per encounter decreased in the ERAS group ($11,619 vs. $8528; p = 0.01). LOS was significantly lower in the ERAS group (4.1 vs. 2.9 days; p = 0.04). CONCLUSIONS: Implementation of the ERAS protocol in gynecologic oncology patients does not lead to increased costs for the patient or hospital system. The decreased contribution margin is likely due to a reduction in per diem payments caused by the reduction in LOS. On a per-patient-day basis, contribution margin was the same for both groups ($2877 vs $2857). The reduction in LOS also created capacity for additional cases, the financial impact of which was not evaluated.

Decreasing opioid use in postoperative gynecologic oncology patients through a restrictive opioid prescribing algorithm.

OBJECTIVE: The objective of this study was to evaluate the impact of a post-surgical restrictive opioid prescribing algorithm (ROPA) in gynecologic oncology patients. METHODS: This cohort study included gynecologic oncology patients undergoing any surgical procedure from 08/2018-7/2019 after implementation of a ROPA. Patients were compared to historical controls managed without a ROPA from 10/2016-9/2017. Patients were educated preoperatively about pain management goals, the ROPA, and opioid disposal. A 4-tiered system was developed to standardize prescriptions at discharge based on surgical complexity and inpatient opioid requirements. Patients were surveyed at their postoperative visit to assess home opioid use and satisfaction. Statistical analysis was performed using SPSS Statistics v.24. RESULTS: 2549 patients met inclusion criteria; 1321 in the historical control group and 1228 in the ROPA group. Demographics, including age, BMI, and performance status were similar. Compared with the control group, the average number of opioid pills prescribed was significantly lower in the ROPA group (30.5 vs 11.3; p < 0.001) along with the morphine milligram equivalents (MME) (152.5 MME vs. 83.3 MME; p < 0.001). The percentage of patients requiring opioid refill within 30 days was similar (13.0% vs. 12.6%; p = 0.71). 95.7% of patients surveyed were satisfied with their pain regimen. The total number of pills prescribed annually decreased from 34,130 in the control group to 13,888 in the ROPA group. CONCLUSIONS: A restrictive prescribing practice allows for a significantly lower number of opioids to be prescribed to postoperative patients while maintaining patient satisfaction. There was no increase in opioid refill requests using a ROPA in patients undergoing surgery.

Niraparib maintenance in frontline management of ovarian cancer: a cost effectiveness analysis.

OBJECTIVES: Niraparib maintenance after frontline chemotherapy for advanced ovarian cancer extends progression free survival. The objective of this study was to determine the cost effectiveness of niraparib maintenance therapy in patients with newly diagnosed ovarian cancer. METHODS: Decision analysis models compared the cost of observation versus niraparib maintenance following chemotherapy for five groups: all newly diagnosed ovarian cancer patients (overall), those with homologous recombination deficiency, those harboring BRCA mutations (BRCA), homologous recombination deficiency patients without BRCA mutations (homologous recombination deficiency non-BRCA), and non-homologous recombination deficiency patients. Drug costs were estimated using average wholesale prices. Progression free survival was estimated from published data and used to estimate projected overall survival. Incremental cost effectiveness ratios per quality adjusted life year were calculated. Sensitivity analyses varying the cost of niraparib were performed. The willingness-to-pay threshold was set at US$100 000 per quality adjusted life year saved. RESULTS: For the overall group, the cost of observation was US$5.8 billion versus $20.5 billion for niraparib maintenance, with an incremental cost effectiveness ratio of $72 829. For the homologous recombination deficiency group, the observation cost was $3.0 billion versus $14.8 billion for niraparib maintenance (incremental cost effectiveness ratio $56 329). Incremental cost effectiveness ratios for the BRCA, homologous recombination deficiency non-BRCA, and non-homologous recombination deficiency groups were $58 348, $50 914, and $88 741, respectively. For the overall and homologous recombination deficiency groups, niraparib remained cost effective if projected overall survival was 2.2 and 1.5 times progression free survival, respectively. CONCLUSIONS: For patients with newly diagnosed ovarian cancer, maintenance therapy with niraparib was cost effective. Cost effectiveness was improved when analyzing those patients with homologous recombination deficiency and BRCA mutations. Efforts should continue to optimize poly-ADP-ribose polymerase utilization strategies.

Pembrolizumab in advanced recurrent endometrial cancer: A cost-effectiveness analysis.

OBJECTIVE: To determine the cost-effectiveness of pembrolizumab in patients with recurrent endometrial cancer that have failed first-line chemotherapy. METHODS: We created a model to evaluate the cost-effectiveness of pembrolizumab compared to pegylated liposomal doxorubicin (PLD) or bevacizumab for the treatment of women with recurrent endometrial cancer who have failed carboplatin and paclitaxel. Microsatellite instability-high (MSI-H) and non-microsatellite instability-high (non-MSI-H) tumors were evaluated. We included 4400 patients in the model; 800 patients were assumed to have MSI-H tumors. Drug costs were calculated using 2016-2017 wholesale acquisition costs, and cost of Grade III-IV toxicities was estimated from clinical experience. Effectiveness was calculated as 2-year overall survival (OS). We calculated incremental cost-effectiveness ratios (ICERs) to determine the cost per 2-year survivor. Univariate sensitivity analyses were performed. The willingness to pay threshold was $100,000 per year of OS. RESULTS: The cost of therapy with PLD and bevacizumab were $33.2 million (M) and $167.9 M, respectively. The cost of pembrolizumab therapy was $318.3 M for non-MSI-H patients compared to $57.9 M for MSI-H patients. For non-MSI-H patients, bevacizumab was cost-effective relative to PLD with an ICER of $153,028, while pembrolizumab was not cost-effective relative to bevacizumab with an ICER of $341,830. For MSI-H patients, pembrolizumab was cost-effective compared to PLD with an ICER of $147,249, while bevacizumab was subjected to extended dominance. Sensitivity analysis revealed that for non-MSI-H patients, one cycle of pembrolizumab would need to cost $7253 or less to be cost-effective. CONCLUSIONS: For patients with MSI-H recurrent endometrial cancers who have failed first-line chemotherapy, pembrolizumab is cost-effective relative to other single agent drugs. To be cost-effective in non-MSI-H patients, the cost of pembrolizumab should decrease substantially.

Timing of robotic hysterectomy after cervical excisional procedure.

INTRODUCTION: While traditional teaching has been to wait 6 weeks between cervical excisional procedure and hysterectomy, studies have produced conflicting evidence, with data supporting a delay of anywhere between 48 hours to 6 weeks depending on surgical approach. Our study sought to evaluate if the time between cervical excisional procedure and robotic hysterectomy impacts peri-operative complication rates. METHODS: A retrospective cohort of patients who underwent robotic hysterectomy from August 2006 to December 2013 for cervical dysplasia or International Federation of Gynecology and Obstetrics (FIGO) 2009 stage IA1-B1 cervical cancer at a single tertiary care center was performed. Patients were categorized into three groups: early surgical intervention (<6 weeks from excisional procedure), delayed surgical intervention (≥6 weeks from excisional procedure), and no excisional procedure. Secondary analysis was performed by hysterectomy type (simple vs radical). Peri-operative outcomes and complications were compared. Statistical analysis included Chi-square, Fisher's exact test, and Wilcoxon rank sum test. RESULTS: A total of 160 patients were identified. Of these, 32 (20.0%) had early surgical intervention, 52 (32.5%) had delayed surgical intervention, and 76 (47.5%) had no excisional procedure. There was no difference between groups in complication rates, including average estimated blood loss (82 vs 55 vs 71 mL; p=0.07), urologic injury (0% in all groups; p=1.0), anemia (3% vs 0% vs 1%; p=0.47), infection (0% vs 2% vs 3%; p=1.0), vaginal cuff separation (0% in all groups; p=1.0), or venous thromboembolism (0% vs 0% vs 1%; p=1.0). Additionally, there were no differences in length of stay (p=0.18) or 30-day readmission rates (p=1.0). Finally, there were no significant differences in peri-operative outcomes when stratified by radical versus simple hysterectomy. DISCUSSION: Waiting 6 weeks between cervical excisional procedure and robotic hysterectomy does not impact peri-operative complication rates. This suggests that the time from excisional procedure should not factor into surgical planning for those who undergo robotic hysterectomy.

The antitumor effects of entinostat in ovarian cancer require adaptive immunity.

BACKGROUND: Ovarian cancer is poorly immunogenic; however, increased major histocompatibility complex class II (MHCII) expression correlates with improved immune response and prolonged survival in patients with ovarian cancer. The authors previously demonstrated that the histone deacetylase inhibitor entinostat increases MHCII expression on ovarian cancer cells. In the current study, they evaluated whether entinostat treatment and resultant MHCII expression would enhance beneficial immune responses and impair tumor growth in mice with ovarian cancer. METHODS: C57BL/6 mice bearing intraperitoneal ID8 tumors were randomized to receive entinostat 20 mg/kg daily versus control. Changes in messenger RNA (mRNA) expression of 46 genes important for antitumor immunity were evaluated using NanoString analysis, and multicolor flow cytometry was used to measure changes in protein expression and tumor-infiltrating immune cells. RESULTS: Entinostat treatment decreased the growth of both subcutaneously and omental ID8 tumors and prolonged survival in immunocompetent C57BL/6 mice. NanoString analysis revealed significant changes in mRNA expression in 21 of 46 genes, including increased expression of the MHCI pathway, the MHCII transactivator (CIITA), interferon γ, and granzyme B. C57BL/6 mice that received entinostat had increased MHCII expression on omental tumor cells and a higher frequency of tumor-infiltrating, CD8-positive T cells by flow cytometry. In immunocompromised mice, treatment with entinostat had no effect on tumor size and did not increase MHCII expression. CONCLUSIONS: In the current murine ovarian cancer model, entinostat treatment enhances beneficial immune responses. Moreover, these antitumor effects of entinostat are dependent on an intact immune system. Future studies combining entinostat with checkpoint inhibitors or other immunomodulatory agents may achieve more durable antitumor responses in patients with ovarian cancer.

Impact of enhanced recovery after surgery (ERAS) protocol on gastrointestinal function in gynecologic oncology patients undergoing laparotomy.

OBJECTIVE: To evaluate the impact of enhanced recovery after surgery (ERAS) on postoperative gastrointestinal function in gynecologic oncology patients. METHODS: This retrospective cohort study compared gynecology oncology patients undergoing non-emergent laparotomy from 10/2016 to 6/2017 managed on an ERAS protocol to a control cohort from the year prior to ERAS implementation. Major changes to postoperative care after ERAS implementation included multimodal analgesia, early feeding, goal-directed fluid resuscitation, and early ambulation. The primary outcome was rate of postoperative ileus, defined as nausea and vomiting requiring nothing-per-mouth status or nasogastric tube (NGT) placement. Secondary outcomes included length of stay (LOS) and 30-day readmission. RESULTS: 376 patients met inclusion criteria; 197 in the control group and 179 in the ERAS group. Patient demographics were similar between groups. Ileus rate was significantly lower in the ERAS group (2.8% vs. 15.7%; p < 0.001), and fewer patients in the ERAS group required NGT placement (2.2% vs. 7.1%; p = 0.06). ERAS remained independently associated with decreased ileus rates when controlling for other patient and surgical factors (OR 0.2; p = 0.01). Epidural use was correlated with a significant increase in ileus risk (OR 2.6; p = 0.03), as was increased Charlson Comorbidity Index (OR 1.2; p < 0.01). LOS was significantly decreased in the ERAS group (2.9 vs. 4.0 days; p = 0.04), while 30-day readmission rates were similar (10.1% vs. 10.7%; p = 0.62). CONCLUSIONS: Implementation of an ERAS protocol significantly decreases the risk of postoperative ileus in gynecologic oncology patients undergoing laparotomy. ERAS also reduced LOS compared to pre-ERAS controls.

The challenge of HPV vaccination uptake and opportunities for solutions: Lessons learned from Alabama.

The human papillomavirus (HPV) vaccine is an important tool for cancer prevention. However, vaccination rates in Alabama, a state with high rates of HPV-related cancers, remain below the national average. Our objective was to develop a comprehensive assessment of HPV vaccination in our state, with the goal to make recommendations for tailored multilevel interventions. A multimodal approach with quantitative and qualitative data was used to determine barriers and facilitators to HPV vaccination in Alabama. This included a survey of pediatric care providers and structured interviews with pediatricians, parents, nurses and community stakeholders. Two separate investigators evaluated the interview transcripts for major themes that occurred in 65% or more interviews. Major barriers included lack of knowledge, concerns about vaccine safety, and the link between the HPV vaccine and sexuality. Qualitative interviews further revealed barriers such as misinformation received from the internet and parental vaccine hesitancy. Opportunities for increasing vaccination include parental education, establishment of a reminder system, increasing access to HPV vaccine providers, and education for providers. Additional facilitators revealed through interviews included: trust in physicians, using the internet or social media to propagate positive messaging, physicians and clinical staff education, utilizing existing technology more effectively, highlighting nurses' roles as partners in HPV prevention, and the potential of schools as a venue for promotion of the vaccine. Our data are consistent with prior research showing major barriers to HPV vaccination. Several recommendations for optimizing HPV vaccination uptake in Alabama on the patient, provider and system level are given.

Predictors of Unplanned Reoperation for Ovarian Cancer Patients From the National Surgical Quality Improvement Program Database.

OBJECTIVES: The aim of this study was to determine preoperative risk factors associated with unplanned reoperation within 30 days for patients undergoing major surgery for primary ovarian cancer using the National Surgical Quality Improvement Program database. METHODS: We conducted a retrospective cohort study utilizing the National Surgical Quality Improvement Program database to identify patients undergoing primary ovarian cancer surgery from 2012 to 2014. Patients who had a reoperation within 30 days of their primary surgery were identified. Demographics and clinical covariates were calculated. Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using univariate and multivariate logistic regression approaches to assess the association. RESULTS: A total of 4260 patients were identified during the study period. One hundred forty-eight patients (3.5%) underwent a reoperation within 30 days of their primary surgery. In univariate analysis, preoperative creatinine 1.5 mg/dL or greater (P = 0.010), smoking (P = 0.003), and both insulin-dependent (P = 0.029) and non-insulin-dependent diabetes mellitus (P = 0.048) were predictive of a reoperation. Multivariate analysis noted that smoking (OR, 1.94; 95% CI, 1.26-2.99), insulin-dependent diabetes mellitus (OR, 2.18; 95% CI, 1.08-4.40), non-insulin-dependent diabetes mellitus (OR, 1.65; 95% CI, 1.01-2.72), and preoperative creatinine (OR, 2.65; 95% CI, 1.26-5.58) were predictive of a reoperation. Age 50 to 60 years was protective against reoperation when compared with age younger than 50 years (OR, 0.54; 95% CI, 0.32-0.90). CONCLUSIONS: Efforts to reduce reoperation rates should focus on identifying high-risk patients by utilizing objective preoperative data. Optimizing their medical status prior to surgery may decrease the reoperation rate in patients with ovarian cancer, thereby improving outcomes and providing a probable cost benefit.

The Impact of Racial, Geographic, and Socioeconomic Risk Factors on the Development of Advanced-Stage Cervical Cancer.

OBJECTIVES: Despite screening, disparities exist in cervical cancer incidence and outcomes. Demographic factors are associated with diagnosis at advanced stage (AS), but less is known about geographic factors. We sought to investigate risk factors for developing AS cervical cancer in Alabama. MATERIALS AND METHODS: We identified women treated for cervical cancer from 2005 to 2015 at our institution. Stages II-IV were considered AS. ZIP codes were categorized by federal Rural-Urban Commuting Area Codes, and 16 historically underserved counties were categorized as Black Belt rural. Using data from the American College of Obstetricians and Gynecologists, we identified women's health provider locations. We explored associations between stage and multiple factors using logistic regression. RESULTS: Of 934 patients, 29.2% were black, 52.7% had AS cancer, and 63.4% lived in urban areas. Average distance to nearest American College of Obstetricians and Gynecologists Fellow in urban, rural, and Black Belt rural areas was 5.0, 10.6, and 13.7 miles, respectively. Black race, public insurance and age of older than 65 years were associated with increased risk of AS cancer. Living in a rural area trended toward higher risk but was not significant. When stratified by race, insurance status and age were associated with AS cancer in white women only. CONCLUSIONS: Living further from a women's health provider or in a rural area was not associated with a higher risk of AS cervical cancer. Black women had a higher risk of AS than white women regardless of age, insurance status, and geography. Disparities in cervical cancer are multifactorial and necessitate further research into socioeconomic, biologic, and systems causes.

High Rates of High-Grade Cervical Dysplasia in High-Risk Young Women With Low-Grade Cervical Cytology.

OBJECTIVE: The aim of the study was to determine rates of cervical intraepithelial neoplasia (CIN) 2 or greater in high-risk, racially diverse, young women with low-grade cytology. MATERIALS AND METHODS: After institutional review board approval, a cross-sectional study of 21- to 24-year-old women with low-grade cytology (atypical squamous cells of undetermined significance, high-risk human papillomavirus+, low-grade squamous intraepithelial lesion, or human papillomavirus+ only) managed with colposcopy at our university-based clinic between May 2011 and April 2013 were identified. Demographics and pathologic data were collected including age, race, parity, smoking status, screening history, and histology. Student t test and χ tests were used to compare women with and without CIN 2 or 3. Univariate analysis was performed with demographic data. RESULTS: One thousand fifty-eight women with a mean (SD) age of 22.5 (1.1) were included. Most patients (59.5%) were parous, 36.1% were smokers, and most (52.9%) were black. These patients were considered high risk because of their lower socioeconomic status, minority status, lack of insurance, or having Medicaid and therefore had limited access to preventative health care. Based on colposcopy, the prevalence of CIN 2+ was 19.1%: 13.9% (95% CI = 11.9-16.1) CIN 2 and 5.1% (95% CI = 3.9-6.6) CIN 3. There was an overall prevalence of 4.7% (95% CI = 3.7%-6.3%) of CIN 3 from excisional pathology from the 157 of 185 patients who returned for a recommended excisional procedure. Smoking (odds ratio = 1.64, 95% CI = 1.2-2.25) and a history of high-grade cytology (odds ratio = 2.06, 95% CI = 1.02-4.01) were associated with CIN 2/3. CONCLUSIONS: High prevalence of CIN 2/3 in young women with low-grade cervical cytology in this population suggests that it may be prudent to consider alternative surveillance such as colposcopy in similar high-risk populations.

The impact of physician burnout on clinical and academic productivity of gynecologic oncologists: A decision analysis.

OBJECTIVE: Physician burnout is associated with mental illness, alcohol abuse, and job dissatisfaction. Our objective was to estimate the impact of burnout on productivity of gynecologic oncologists during the first half of their career. METHODS: A decision model evaluated the impact of burnout on total relative value (RVU) production during the first 15years of practice for gynecologic oncologists entering the workforce from 2011 to 2015. The SGO practice survey provided physician demographics and mean annual RVUs. Published data were used to estimate probability of burnout for male and female gynecologic oncologists, and the impact of depression, alcohol abuse, and early retirement. Academic productivity was defined as annual PubMed publications since finishing fellowship. RESULTS: Without burnout, RVU production for the cohort of 250 gynecologic oncologists was 26.2 million (M) RVUs over 15years. With burnout, RVU production decreased by 1.6 M (5.9% decrease). Disproportionate rates of burnout among females resulted in 1.1 M lost RVUs for females vs. 488 K for males. Academic production without burnout was estimated at 9277 publications for the cohort. Burnout resulted in 1383 estimated fewer publications over 15years (14.9%). CONCLUSIONS: The impact of burnout on clinical and academic productivity is substantial across all specialties. As health care systems struggle with human resource shortages, this study highlights the need for effective burnout prevention and wellness programs for gynecologic oncologists. Unless significant resources are designated to wellness programs, burnout will increasingly affect the care of our patients and the advancement of our field.

Preventing human papillomavirus-related cancers: we are all in this together.

Human papillomavirus-related cancers, which include cervical, vulvovaginal, anal, and oropharyngeal cancers, are on the rise in the United States. Although the human papillomavirus vaccine has been on the market for 10 years, human papillomavirus vaccination rates are well below national goals. Research identified many barriers and facilitators to human papillomavirus vaccination, and provider recommendation remains the most important factor in parental and patient decisions to vaccinate. While much of the burden of human papillomavirus vaccine provision falls on pediatricians and primary care providers, they cannot do it alone. As clinicians who care for a large proportion of human papillomavirus-related conditions, obstetrician-gynecologists and other women's health care providers must share the responsibility for vaccination of eligible patients. Obstetrician-gynecologists can support the efforts to eradicate human papillomavirus-related disease in their patients and their families via multiple avenues, including providing the human papillomavirus vaccine and being community leaders in support of vaccination.

Does Obesity Affect Pathologic Agreement of Initial and Final Tumor Grade of Disease in Endometrial Cancer Patients?

OBJECTIVES: The objectives of this study were to compare preoperative and postoperative tumor grade to determine if surgical staging decisions for endometrial cancer based on preoperative biopsy are feasible and whether obesity affects the agreement. METHODS: A retrospective cohort study of women with endometrial cancer between January 2010 and December 2011 was performed. Demographics, stage of final pathology, biopsy method, preoperative and postoperative tissue grade, and histology were abstracted and stratified by patient body mass index (obese ≥30 kg/m and nonobese <30 kg/m). Patients with incomplete records or uterine sarcoma were excluded. The agreement between preoperative and postoperative tumor grade for all patients and in obese and nonobese patients was determined using weighted κ statistics. RESULTS: Four hindered forty-five patients were included: 161 nonobese patients and 284 obese patients. The proportion of preoperative sampling via office biopsy and dilation and curettage was similar in each cohort. Overall, the agreement between preoperative and postoperative pathology was only fair (weighted κ = 0.21). Stratified by body mass index, the agreement between preoperative and postoperative grade remains fair in obese and slight in nonobese patients (weighted κ = 0.21 and 0.19, respectively). Substantial increases in tumor grade from preoperative to postoperative pathologic specimens occurred in both cohorts. CONCLUSIONS: Obesity does not appear to significantly alter the correlation between preoperative biopsy and final tumor grade. With only fair correlation between preoperative and postoperative pathologic evaluation, utilization of preoperative biopsy pathology results as a triage tool for surgical staging should be avoided. However, the discordance between preoperative and postoperative pathology in favor of a higher grade on final pathology in both groups may cause some surgeons to favor staging.

Targeting the Wnt/ß-catenin pathway in primary ovarian cancer with the porcupine inhibitor WNT974.

Preclinical studies in ovarian cancer have demonstrated upregulation of the Wnt/ß-catenin pathway promoting tumor proliferation and chemoresistance. Our objective was to evaluate the effect of the Wnt/ß-catenin pathway inhibitor, WNT974, in primary ovarian cancer ascites cells. Ascites cells from patients with papillary serous ovarian cancer were isolated and treated with 1 µM WNT974±100 µM carboplatin. Viability was evaluated with the ATPlite assay. The IC50 was calculated using a dose-response analysis. Immunohistochemistry (IHC) was performed on ascites cells and tumor. Expression of R-spondin 2 (RSPO2), RSPO3, PORCN, WLS, AXIN2, and three previously characterized RSPO fusion transcripts were assessed using Taqman assays. Sixty ascites samples were analyzed for response to WNT974. The ascites samples that showed a decrease in ATP concentration after treatment demonstrated no difference from the untreated cells in percent viability with trypan blue staining. Flow cytometry demonstrated fewer cells in the G2 phase and more in the G1 and S phases after treatment with WNT974. Combination therapy with WNT974 and carboplatin resulted in a higher percentage of samples that showed ≥30% reduction in ATP concentration than either single drug treatment. IHC analysis of Wnt pathway proteins suggests cell cycle arrest rather than cytotoxicity after WNT974 treatment. QPCR indicated that RSPO fusions are not prevalent in ovarian cancer tissues or ascites. However, higher PORCN expression correlated to sensitivity to WNT974 (P=0.0073). In conclusion, WNT974 produces cytostatic effects in patient ascites cells with primary ovarian cancer through inhibition of the Wnt/ß-catenin pathway. The combination of WNT974 and carboplatin induces cytotoxicity plus cell cycle arrest in a higher percentage of ascites samples than with single drug treatment. RSPO fusions do not contribute to WNT974 sensitivity; however, higher PORCN expression indicates increased WNT974 sensitivity.

Early warning score: An indicator of adverse outcomes in postoperative patients on a gynecologic oncology service.

OBJECTIVE: In 2014, our hospital implemented an early warning score (EWS) to identify inpatients at risk for clinical deterioration. EWS≥8 is associated with ≥10% mortality in medical admissions. Since postoperative hemodynamic changes may alter EWS, we evaluated EWS in post-laparotomy patients. METHODS: Gynecologic oncology patients admitted for laparotomy from 9/1/2014 to 7/31/2015 were categorized by highest EWS during admission: <5, 5-7, and ≥8. The primary outcome was a composite including death, ICU transfer, rapid response team activation, pulmonary embolus, sepsis, and reoperation. For patients with the composite, highest EWS prior to that outcome was evaluated. Secondary outcomes were length of stay (LOS), readmission, and transfusion. Groups were compared using chi-square test for trend, analysis of variance, and Kruskal-Wallis tests. A receiver operating characteristic (ROC) curve estimated the association between EWS and the composite outcome. RESULTS: 411 patients were included: 217 (52.8%) with EWS<5, 151 (36.7%) with EWS 5-7, and 43 (10.5%) with EWS≥8. The composite occurred in 32.6% of patients with EWS≥8, 7.3% with EWS 5-7, and 0% with EWS<5 (p<0.01). EWS≥8 was associated with longer LOS, higher readmission rate, and more transfusions. For the composite, the area under the ROC curve was 0.89 (95% CI 0.84-0.94). EWS≥5 had 100% sensitivity and 56.2% specificity for the primary outcome; EWS≥8 had 56.0% sensitivity and 92.5% specificity for the primary outcome. CONCLUSIONS: EWS≥5 after laparotomy is associated with adverse outcomes. Future studies should evaluate the ability of EWS to predict and prevent these outcomes.